Updated efficacy and safety of HLX02 versus reference trastuzumab in metastatic HER2-positive breast cancer: A randomized phase III equivalence trial

Aim: Equivalence between HLX02 and trastuzumab sourced from the European Union (EU-trastuzumab), in combination with docetaxel, was demonstrated in a phase III study. This study aimed to evaluate the long-term efficacy and safety data after 3 years of follow-up. Methods: Patients with previously untreated, HER2-positive metastatic breast cancer received intravenous HLX02 or EU-trastuzumab (initial dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks for up to 12 months) in combination with docetaxel. Primary endpoint was the overall response rate up to week 24 (ORR₂₄). Secondary endpoints including updated overall survival (OS), progression-free survival (PFS), safety and immunogenicity are reported in this long-term follow-up analysis. Results: After a median follow-up duration of 35.0 months, 270 out of the 649 enrolled patients had died; 128 (39.5 %) in the HLX02 and 142 (43.7 %) in the EU-trastuzumab group. Median OS was 37.3 (95 % CI 36.2, not evaluable [NE]) months and not reached (95 % CI 34.2, NE) (stratified HR 0.86 [95 % CI 0.68, 1.10]; p = 0.229), with a 3-year OS rate of 57.5 % and 54.0 %, respectively. Median PFS at this long-term follow-up assessment was 11.7 (95 % CI 11.5, 12.1) months for the HLX02 group and 10.6 (95 % CI 9.5, 11.7) months for the EU-trastuzumab group (stratified HR 0.86 [95 % CI 0.69, 1.06]; p = 0.158). No new safety concerns were reported until the end of the survival follow-up. Conclusion: Long-term efficacy and safety were consistent with the previous findings. No clinically meaningful differences between HLX02 and reference trastuzumab were demonstrated. Clinical trial registration: Chinadrugtrials.org CTR20160526 (September 12, 2016), ClinicalTrials.gov NCT03084237 (March 20, 2017), EudraCT 2016-000206-10 (April 27, 2017).